Resveratrol Prevents Right Ventricle Remodeling and Dysfunction in Monocrotaline-Induced Pulmonary Arterial Hypertension with a Limited Improvement in the Lung Vasculature

Abstract

Pulmonary arterial hypertension (PAH) is a life-threatening disease that is characterized by an increase in pulmonary vascular pressure, leading to ventricular failure and high morbidity and mortality. Resveratrol, a phenolic compound and a sirtuin 1 pathway activator, has known dietary benefits and is used as a treatment for anti-inflammatory and cardiovascular diseases. Its therapeutic effects have been published in the scientific literature; however, its benefits in PAH are yet to be precisely elucidated. Using a murine model of PAH induced by monocrotaline, the macroscopic and microscopic effects of a daily oral dose of resveratrol in rats with PAH were evaluated by determining its impact on the lungs and the right and left ventricular function. While most literature has focused on smooth muscle cell mechanisms and lung pathology, our results highlight the relevance of therapy-mediated improvement of right ventricle and isolated cardiomyocyte physiology in both ventricles. Although significant differences in the pulmonary architecture were not identified either micro- or macroscopically, the effects of resveratrol on right ventricular function and remodeling were observed to be beneficial. The values for the volume, diameter, and contractility of the right ventricular cardiomyocytes returned to those of the control group, suggesting that resveratrol has a protective effect against ventricular dysfunction and pathological remodeling changes in PAH. The effect of resveratrol in the right ventricle delayed the progression of findings associated with right heart failure and had a limited positive effect on the architecture of the lungs. The use of resveratrol could be considered a future potential adjunct therapy, especially when the challenges to making a diagnosis and the current therapy limitations for PAH are taken into consideration.

ACE Inhibitory and Antihypertensive Activities of Wine Lees and Relationship among Bioactivity and Phenolic Profile

“…In this sense, winery by-products have been successfully used to obtain antioxidant [ 31 ], antimicrobial [ 32 ], anti-inflammatory [ 33 ], antihyperglycemic [ 34 ], or antihypertensive compounds [ 14 , 16 , 17 , 35 ]. For instance, extracts rich in phenolic compounds (proanthocyanidins or resveratrol), with antihypertensive properties in both rats and humans, have been extracted from stem, grape seeds, or skin, respectively [ 13 , 15 , 16 , 17 , 36 , 37 , 38 ]. However, to our knowledge, no studies have been performed to evaluate whether WL can present ACEi or antihypertensive properties.…”

“…Grapes are one of the world’s largest fruit crops and the wine production process generates large amounts of by-products [ 12 ]. Some winery by-products, such as grape seeds and skin, have already been used as a source for the extraction of phenolic compounds with numerous health benefits, including antihypertensive properties [ 13 , 14 , 15 , 16 , 17 ]. However, the presence of antihypertensive compounds in other winery by-products as wine lees (WL) remains unexplored.…”

Mitochondrial and Sarcoplasmic Reticulum Interconnection in Cardiac Arrhythmia

“…Other antioxidants, such as quercetin and resveratrol, have been useful in preventing cellular damage and preserving mitochondrial functioning upon challenge with insults in vitro models, such as I/R ( Lozano et al, 2019 ), and in reducing right-heart remodeling and dysfunction in a murine model of pulmonary arterial hypertension ( Vázquez-Garza et al, 2020 ). Regarding arrhythmias, treatment with quercetin has proven useful in preventing platelet aggregation and arrhythmias in an I/R murine model.…”

“…It was previously thought that antioxidants like quercetin and resveratrol, due to their low bioavailability and non-specificity to any tissue, would make them poor candidates for new therapies ( Formica and Regelson, 1995 ). This is backed by the fact that only limited benefits have been found when using such therapies ( Askari et al, 2012 ; Wilson et al, 2016 ; Vázquez-Garza et al, 2020 ). Nonetheless, similar to the gene therapy described previously, the development of nanomaterials capable of packaging the components, protecting them from degradation, and directing them to a specific tissue places these often-dismissed compounds back on the table.…”

Resveratrol Protects Cardiac Tissue in Experimental Malignant Hypertension Due to Antioxidant, Anti-Inflammatory, and Anti-Apoptotic Properties

“…Several studies reported that resveratrol possessed antioxidant [ 23 ], anti-inflammatory [ 24 ], and proapoptotic activity [ 25 ]. Dietary polyphenol, resveratrol, has potential to improve endothelial dysfunction and decrease overall blood pressure [ 5 , 26 ]. In the hypertensive condition, resveratrol decreases vascular oxidative stress by scavenging H 2 O 2 and preventing oxidative stress-induced endothelial cell death [ 27 ].…”